Manifestation of ischemic preconditioning and its mechanisms during percutaneous transluminal coronary angioplasty (PTCA) was evaluated. Twenty-two patients with angina pectoris, who had one-vessel coronary artery disease of the proximal left anterior descending artery but without visual collateral circulation, underwent elective PTCA performed by balloon inflations of 90 s, repeated three times or more. Changes in standard 12-lead electrocardiogram, hemodynamics and oxygen saturation of the great cardiac vein by a fiber-optic catheter were analyzed. Anginal chest pain occurred in 21 patients (95%) during the first balloon inflation, and in only 9 patients (41%) during the third inflation. In comparison with the first inflation, the third produced less shifts in ST junction (p < 0.01) and peak T (p < 0.01), which were measured and averaged by 4 chest leads from V2 to V5. The heart rate-blood pressure product during the third inflation was equivalent to that during the first. The great cardiac vein oxygen saturation decreased equally during the first and third inflations. However, the ratio of the saturation at reactive hyperemia after balloon deflation to baseline was higher (p < 0.01) in the third than in the first inflation. The adenosine content of the great cardiac vein measured in 11 patients just prior to balloon deflation was also higher (p < 0.05) in the third inflation than the value in the first. Repeated coronary artery occlusion during PTCA could cause ischemic preconditioning, which may be derived from mechanisms common to accelerated reactive hyperemia, for example an increase in intrinsic adenosine levels.